Ephrin-B3 is a cell-surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development.

Ephrin-B3 binds to Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. It may play a pivotal role in forebrain function. Ephrin-B3 has been shown to bind to, and induce the collapse of, commissural axons/growth cones in vitro. It may also play a role in constraining the orientation of longitudinally projecting axons.